Namenda "Mildly Beneficial" for Lewy-Body Dementia

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Memantine might lessen deterioration and improve behavioural symptoms in patients with a neurodegenerative disease known as dementia with Lewy bodies (DLB)*, and has the potential to become a treatment option for these patients, according to the largest study of memantine in patients with Lewy-body-related dementias, published in an Article Online First and in the October edition of The Lancet Neurology (www.thelancet.com).

The drug memantine blocks the excessive actions of the brain chemical glutamate without affecting the activity of glutamate receptors that are essential for normal brain function. Memantine has shown beneficial effects in Alzheimer's disease and could be a potential treatment for other brain disorders that may involve an excess of glutamate stimulation, such as Lewy-body-related dementias (Parkinson's disease dementia [PDD] and DLB).

In this study, an international team led by Murat Emre from Istanbul University in Turkey investigated the safety and efficacy of memantine for the treatment of mild to moderate PDD and DLB. Over 6 months, 199 patients (121 PDD and 78 DLB) from 30 specialist centres across Europe were randomly assigned to receive memantine (20 mg) or placebo once a day. Functional, behavioural, cognitive, and global outcome measures were recorded at the start of the study and at the end of weeks 4, 12, 16, and 24. Additionally, caregivers were interviewed to assess the strain on carers during the study.

After 24 weeks, more patients treated with memantine showed improvement in clinical status, as observed by clinicians, compared with the placebo group.

Overall, more DLB patients who were taking memantine had a favourable response, and this group showed a significantly greater improvement in global clinical status and behavioural symptoms than those taking placebo. However, no significant differences were found between the two treatments in patients with PDD.

Additionally, there were no significant differences in treatment outcomes associated with activities of daily living, motor symptoms, or caregiver burden.

Memantine was generally well tolerated and side-effects were mild and similar between the two treatment groups. The most common serious adverse events were stroke (three in the memantine group), falls (two in the memantine group; one in the placebo group), and worsening of dementia (two in the memantine group).

Patients with DLB seemed to benefit more from memantine than those with PDD and the authors suggest that this might be because DLB has more pathological similarities to Alzheimer's disease than does PDD.

They conclude: "On the basis of the results of this study, memantine might be a treatment option in patients with mild to moderate DLB."

In a Comment, Laura Marsh from Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Texas, USA, says that the study highlights the complexity of the clinical management of patients with Lewy-body-related dementias. She points out that memantine is a symptomatic treatment and not a cure and emphasises the urgent need for pharmacological treatments that address cognitive impairment in Parkinson's disease and related disorders before the development of frank dementia.


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http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2810%2970194-0/abstract

Murat Emre MD, Magda Tsolaki MD, Prof Ubaldo Bonuccelli MD, Prof Alain Destée MD, Prof Eduardo Tolosa MD, Alexandra Kutzelnigg MD, et al. Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. The Lancet Neurology, Early Online Publication, 23 August 2010


Background
Previous studies have suggested that patients with Lewy-body-related dementias might benefit from treatment with the N-methyl D-aspartate receptor antagonist memantine, but further data are needed. Therefore, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB).

Methods
Patients (≥50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey. They were randomly assigned to placebo or memantine (20 mg per day) according to a computer-generated list. Patients and all physicians who had contact with them were masked to treatment assignment. No primary endpoint was defined. Safety analyses were done for all patients who took at least one dose of memantine or placebo, and efficacy analyses were done for all patients who had at least one valid postbaseline assessment. This trial is registered with ClinicalTrials.gov, number NCT00855686.

Findings
Of the 199 patients randomly assigned to treatment, 34 with DLB and 62 with PDD were given memantine, and 41 with DLB and 58 with PDD were given placebo. 159 (80%) patients completed the study: 80 in the memantine group and 79 in the placebo group. 93 patients treated with memantine and 97 patients treated with placebo were included in the efficacy analysis. At week 24, patients with DLB who received memantine showed greater improvement according to Alzheimer's disease cooperative study (ADCS)-clinical global impression of change scores than did those who received placebo (mean change from baseline 3·3 vs 3·9, respectively, difference −0·6 [95% CI −1·2 to −0·1]; p=0·023). No significant differences were noted between the two treatments in patients with PDD (3·6 with memantine vs 3·8 with placebo, −0·1 [−0·6 to 0·3]; p=0·576) or in the total population (3·5 with memantine vs 3·8 with placebo, −0·3 [−0·7 to 0·1]; p=0·120). Neuropsychiatric-inventory scores showed significantly greater improvement in the memantine group than in the placebo group (−4·3 vs 1·7, respectively, −5·9 [−11·6 to −0·2]; p=0·041) in patients with DLB, but not in those with PDD (−1·6 vs −0·1, respectively, −1·4 [−5·9 to 3·0]; p=0·522) or in the total patient population (−2·6 vs 0·4, respectively, −2·9 [−6·3 to 0·5]; p=0·092). In most of the cognitive test scores, ADCS-activities of daily living, and Zarit caregiver burden scores, there were no significant differences between the two treatment groups in any of the study populations. The incidence of adverse events and number of discontinuations due to adverse events were similar in the two groups. The most common serious adverse events were stroke (n=3 in memantine group), falls (n=2 in memantine group; n=1 in placebo group), and worsening of dementia (n=2 in memantine group).

Interpretation
Memantine seems to improve global clinical status and behavioural symptoms of patients with mild to moderate DLB, and might be an option for treatment of these patients.